Effects on α- and β-cell function of sequentially adding empagliflozin and linagliptin to therapy in people with type 2 diabetes previously receiving metformin: An exploratory mechanistic study.

Aims The aim of the study was to investigate the effect of sequential treatment escalation with empagliflozin and linagliptin on laboratory markers of alpha- and beta cell function in patients with type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin monotherapy. Methods Forty-four patients with T2DM received 25 mg empagliflozin for a duration of one month in an open-label fashion (treatment period (TP 1). Thereafter, patients were randomised to a double-blind add-on therapy with linagliptin 5 mg or placebo (TP 2) for one additional month. Alpha- and beta cell function were assessed with a standardised liquid meal test (LMT) and an intravenous (iv.) glucose challenge. Effi…

Endothelial Function and Arterial Stiffness in Uncomplicated Type 1 Diabetes and Healthy Controls and the Impact of Insulin on These Parameters during an Euglycemic Clamp

BACKGROUND In addition to its role in glucose metabolism, insulin has shown to exert numerous vascular effects, and an impaired vascular function of insulin is assumed to be a major contributor in the development of vascular complications. Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to investigate the effect of insulin on arterial stiffness and parameters of endothelial function in patients with type 1 diabetes and healthy control subjects. METHODS Fourteen patients with type 1 diabetes (six male, eight female) with a mean age of 36.6 +/- 11.8 …

Prädiktive genetische Untersuchungen: Individualisierung von Diagnostik und Therapie bei Familien mit multipler endokriner Neoplasie Typ II

BACKGROUND AND OBJECTIVE When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. PATIENTS AND METHODS The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic i…

Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk—the PIOSTAT Study

We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance, plasma adiponectin, postprandial plasma glucose, insulin, and intact proinsulin levels in a nondiabetic population at cardiovascular risk. One hundred twenty-five nondiabetic patients at cardiovascular risk were randomized to pioglitazone (PIO), pioglitazone and simvastatin (PIO/SIM), or simvastatin (SIM) treatments. Blood samples were taken for the measurement of adiponectin and lipid levels. In addition, an oral glucose load with the measurements of glucose, insulin, and intact proinsulin levels was performed. Adiponectin levels increased from 14.0 ± 8.2 to 27.6 ± 14.5 …

The influence of local capsaicin treatment on small nerve fibre function and neurovascular control in symptomatic diabetic neuropathy.

Topical treatment with capsaicin cream has been shown to be successful in the treatment of different symptomatic nerve disorders like diabetic neuropathy. Conflicting data exist on the effect of capsaicin on nerve function and neurovascular control especially in patients with diabetic neuropathy. The aim of this pilot study was to investigate the impact of topical capsaicin application on small nerve fibre function and neurovascular control. Capsaicin cream was applied to the feet of 13 patients with symptomatic diabetic neuropathy over a period of 8 weeks. Before and during the treatment period, we investigated the total symptoms score, the vibration, thermal (heat and cold) and pain perce…

Pioglitazone in addition to metformin improves erythrocyte deformability in patients with Type 2 diabetes mellitus

The aim of the present study was to compare the effect of PIO (pioglitazone) or GLIM (glimepiride) on erythrocyte deformability in T2DM (Type 2 diabetes mellitus). The study covered 23 metformin-treated T2DM patients with an HbA1c (glycated haemoglobin) >6.5%. Patients were randomized to receive either PIO (15 mg, twice a day) or GLIM (1 mg, twice a day) in combination with metformin (850 mg, twice a day) for 6 months. Blood samples were taken for the measurement of fasting glucose, HbA1c, fasting insulin, intact proinsulin, adiponectin and Hct (haematocrit). In addition, the erythrocyte EI (elongation index) was measured using laser diffractoscopy. Both treatments significantly impr…

The effect of human proinsulin C-peptide on erythrocyte deformability in patients with Type I diabetes mellitus.

Aims/hypothesis. In recent years, evidence has arisen that proinsulin C-peptide exerts biological effects especially on microcirculation, e. g. C-peptide has been shown to increase skin microcirculation in patients with Type I (insulin-dependent) diabetes mellitus and to activate endothelial nitric oxide synthase. This study aimed to investigate the influence of proinsulin C-peptide on erythrocyte deformability which was assessed by means of laser diffractoscopy. Methods. Blood samples from healthy control subjects (n = 10) and Type I diabetic patients (n = 15) completely deficient of C-peptide were analysed at shear stresses ranging from 0.3 to 30 Pa. Results. Erythrocyte deformability was…

Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial β-cell protection in individuals with type 2 diabetes

AIM Postprandial release of intact proinsulin (IP) is an independent marker for beta-cell dysfunction in patients with type 2 diabetes. This open-label, parallel-group, two-arm, pilot study compared the beta-cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin. MATERIAL AND METHODS Overall, 28 insulin-naive type 2 diabetes subjects (mean +/- SD age, 61.5 +/- 6.7 years; diabetes duration, 9.8 +/- 6.5 years; HbA1c, 7.1 +/- 0.5%; BMI, 30.7 +/- 4.3 kg/m(2)) treated with metformin and sulfonylurea were randomized to add once-daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre- …

Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals.

It is expected that microvascular blood flow might be affected by blood glucose, blood insulin and C-peptide levels. In our investigation skin microvascular blood flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37 degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight. The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous oxygen electrode at a temperature of 44 degrees C. The microvascular response to acetylcholine was investigated before the start of the ingestion period and after 30 minutes. In addition, the capillary blood cell v…

α-Lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products

Advanced glycation end products (AGEs) have been identified as relevant mediators of late diabetic complications such as atherosclerotic disease. The endothelial migration of monocytes is one of the first steps in atherogenesis and monocyte-endothelial interaction itself is linked to the expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1). Recently, stimulation of VCAM-1 by AGEs has been demonstrated. Since endothelial stimulation by AGEs is followed by generation of oxygen free radicals with subsequent activation of nuclear transcription factor kappaB, we investigated the influence of alpha-lipoic acid on the expression of VCAM-1 and monocyte adherence to endot…

Peripheral Leptin Levels in Narcoleptic Patients

Narcolepsy is a severe sleep disorder that in most patients is characterized by the deficiency of central orexin. Clinically, narcolepsy is associated with obesity. Currently, there is a literature controversy about the potential alteration of leptin levels in narcoleptic patients. Theoretically, diminished leptin levels could partially contribute to the observed overweight of patients. Two studies have reported decreased leptin levels, whereas a larger, recent study failed to detect differences between patients and controls.To help settle the controversy, we have measured peripheral leptin levels in 42 narcoleptic patients and in 31 body mass index-matched controls.No significant differenc…

The physiological impact of proinsulin C-peptide

Abstract The proinsulin C-peptide fulfills an important function in the biosynthesis of insulin by facilitating the formation of the correct secondary and tertiary structure of the hormone. C-peptide and insulin are released in equimolar amounts to the circulation but C-peptide has generally been considered to be biologically inert. However, recent studies indicate that C-peptide administration to type 1 diabetes patients is accompanied by improved renal function, amelioration of autonomic dysfunction, stimulated tissue glucose utilization and augmented skin and muscle blood flow. The cellular mechanisms underlying these effects may be related to C-peptide's capacity to stimulate both Na + …

Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function

Diabet. Med. 29, 1115–1118 (2012) Abstract Aims  The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy. Methods  Forty-four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA1c < 53 mmol/mol (7.0%), age 30–65 years. Patients were randomized to receive additional liraglutide or to remain on metformin monotherapy. After 6 weeks (1.2 mg) and after 12 weeks (1.8 mg), venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function. In addition, retinal microvascular endothelia…

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type …

Encapsulation of Langerhans' islets: Microtechnological developments for transplantation

There is an increasing trend to apply microsystems and microfluidics to solve medical and biomedical tasks. Microfluidic modules are used to modify and manipulate cells and cell clusters for therapeutic applications. Specifically, a method and technical system for encapsulation of Langerhans' islets as an option for the future treatment of diabetes mellitus is described. Type-1 diabetes patients suffer from an absolute lack of the hormone insulin caused by an autoimmune process destroying the Langerhans' islets. One way to restore glucose-dependent insulin secretion is the transplantation of human pancreatic islet cells (85% beta cells) from cadaveric donors. However, to prevent the rejecti…

Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone.

Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data ar…

The influence of isolated small nerve fibre dysfunction on microvascular control in patients with diabetes mellitus

Aim The aim of the study was to investigate the influence of isolated small nerve fibre dysfunction on microvascular skin blood flow and transcutaneous oxygen tension in patients with diabetes mellitus. Methods  Small nerve fibre dysfunction was assessed by the measurement of thermal and pain perception thresholds. Patients with evidence of large fibre disturbances as evaluated by means of vibration perception threshold were excluded from the study. Microvascular blood flow was investigated with laser-Doppler-fluxmetry (LDF) following stimulation with acetylcholine and mild thermal injury. Results  Diabetic patients with small nerve fibre injury showed a significantly reduced increase in th…

Impact of environmental temperature on skin thickness and microvascular blood flow in subjects with and without diabetes.

Glucose measurement from different skin areas might be influenced by changes in skin texture due to several environmental confounders. Our study was performed to investigate the effect of changes in ambient temperature on skin thickness and microvascular skin blood flow in subjects with and without diabetes at the lower forearm.Thirteen subjects with diabetes and seven without diabetes participated in the study. The investigations were performed in a temperature- and humidity-controlled climatic chamber (EMPA, St. Gallen, Switzerland). Starting at 25 degrees C, the environmental temperature was changed in 4 degrees C steps every 40 min. Skin thickness was measured by an ultrasonic reflectio…

Pilot study for the evaluation of morphological and functional changes in retinal blood flow in patients with insulin resistance and/or type 2 diabetes mellitus.

Background: The aim of this study was to investigate early morphological and functional pathology in the retinal micro-circulation in patients with insulin resistance and/or type 2 diabetes mellitus (T2DM). Methods: Fifty-four subjects, without features of retinopathy under ophthalmological investigation, were recruited for study participation and were classifed into three study groups according to their metabolic staging: (1) Group C comprised nondiabetic, insulin-sensitive subjects with a BMI &lt;28kg/m2; (2) Group IR comprised nondiabetic, insulin-resistant, obese subjects with a BMI ≥28 kg/m2; and (3) Group DM comprised patients with manifested T2DM. Retinal microvascular blood flow was…

Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide.

There is increasing evidence for biological functions of human C-peptide. Recently, we have described that proinsulin C-peptide increases nutritive capillary blood flow and restores erythrocyte deformability in type 1 diabetic patients, whereas it has no such effect in non-diabetic subjects. The aim of the current study was to elucidate cellular mechanisms of this vasodilator effect in vitro by measuring the nitric oxide (NO)-mediated increase of cGMP production in a RFL-6 reporter cell assay and by demonstrating endothelial calcium influx with the Fluo-3 technique. C-peptide increased the release of NO from endothelial NO synthase (eNOS) in bovine aortic endothelial cells in a concentratio…

Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2.

The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2.A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months.HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p.0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p.0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p…

Elevated peripheral visfatin levels in narcoleptic patients.

OBJECTIVE: Narcolepsy is a severe sleep disorder that is characterized by excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent discoveries indicate that the major pathophysiology is a loss of hypocretin (orexin) producing neurons due to immunologically mediated degeneration. Visfatin is a recently described proinflammatory adipokine. It is identical to the immune modulating pre-B-cell colony enhancing factor (PBEF). Our study examines the hypothesis that visfatin levels are altered in narcoleptic patients. METHODS: For the analysis, a total of n = 54 patients (n = 18 males and n = 36 females) with the diagnosis of narcolepsy according to DSM-IV and the Internatio…

Microvascular effects of the inhibition of dipeptidylpeptidase IV by linagliptin in nondiabetic hypertensive patients

Recent studies suggest vascular benefits of dipeptidylpeptidase IV (DPP-IV) inhibition in patients with diabetes mellitus. Only little is known about potential vascular effects of DPP-IV inhibitors in nondiabetic individuals. The aim of this study was to investigate the effect of DPP-IV inhibition in a nondiabetic hypertensive population.This was a double-blinded, randomized, placebo-controlled, mechanistic study, comparing microvascular effects of the DPP-IV inhibitor linagliptin with placebo in nondiabetic individuals with a history of arterial hypertension. Twenty-one patients received 5 mg linagliptin (5 women; age 67.6 ± 6.0 years; mean ± SD), whereas 22 patients were randomized to pla…

Serum levels of substance P are decreased in patients with type 1 diabetes.

Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml; p<0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Fu…

Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain

What is already known about this subject • Despite encouraging effects of N-methyl-D-aspartate (NMDA) receptor antagonists in reducing neuropathic pain of different aetiologies, the clinical use of these agents has been limited by their mainly psychotropic side-effects. • In a recent study in healthy volunteers, CNS 5161, a novel noncompetetive NMDA receptor antagonist, was well tolerated up to a dosage of 2000 µg without psychotropic side-effects. • This is the first study to evaluate the maximal tolerated dosage of CNS 5161 and to gain experience about the analgesic effect of CNS 5161 in patients with different pain syndromes. What this study adds • In patients with neuropathic pain CNS 5…

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk.

We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4±6.5 years; body mass index [BMI] 29.2±4.1 kg/m2; mean±SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator …

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy

In patients with diabetes mellitus (DM), early retinal microvascular alterations can be observed even before the clinical diagnosis of diabetic retinopathy. This study aimed to investigate morphological and functional changes in retinal microvascular blood flow in type 1 diabetic patients with and without peripheral neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with flicker light. PNP was assessed using the neuropathy disability score (NDS) and by the evaluation of the vibration perception threshold (V…

Establishment of a quantitative RT-pCR for detection of vascular cell adhesion molecule-1 transcripts in endothelial cells after stimulation with advanced glycation endproducts.

Advanced glycation endproducts (AGE) are supposed to increase endothelial expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1) by inducing an intracellular stress with subsequent activation of nuclear transcription factor NF-kappa-B. Quantitative analysis of VCAM-1-transcription has not been demonstrated concerning this topic. Thus, the aim of this study was to establish quantitative reverse transcription polymerase chain reaction (RT-PCR) assays using a spacer gene in order to measure the amounts of specific mRNA for VCAM-1 in human umbilical vein endothelial cells (HUVEC) which were stimulated with AGE-albumin (AGE-BSA). A recombinant RNA-standard was synthesiz…

Evaluation of CGMS® During Rapid Blood Glucose Changes in Patients with Type 1 Diabetes

CGMS (Medtronic Minimed, Duesseldorf, Germany) allows continuous glucose monitoring. Recent studies with invasive monitoring techniques revealed discrepancies in blood glucose measurements obtained from different anatomical sites compared with those from the fingertip. The aim of this study was to investigate the CGMS and a device for alternative site testing (AST) during dynamic blood glucose changes and to compare these results with fingertip measurements.Twelve patients with type 1 diabetes (seven women, five men; age, 33.3 +/- 8.7 years) received a 75-g oral glucose load. Insulin was applied intravenously (rapid glucose decline) or subcutaneously (moderate glucose decline) in a dosage b…

Investigation of insulin resistance in narcoleptic patients: dependent or independent of body mass index?

Alice Engel1,2, Jana Helfrich1, Nina Manderscheid1, Petra B Musholt3, Thomas Forst3, Andreas Pf&amp;uuml;tzner3, Norbert Dahmen1,21Department of Psychiatry, University of Mainz, Germany; 2Fachklinik Katzenelnbogen, Katzenelnbogen, Germany; 3IKFE, Institute for Clinical Research and Development, Mainz, GermanyBackground: Narcolepsy is a severe sleep-wake cycle disorder resulting in most cases from a lack of orexin, the energy balance-regulating hormone. Narcoleptic patients have been reported to suffer from an excess morbidity of Type 2 diabetes, even after correction for their often elevated body mass index.Methods: To explore whether narcolepsy is specifically associated with a propensity …

Bone Mineral Density and Bone Metabolism in Diabetes Mellitus

The effect of diabetes mellitus on bone metabolism and bone mineral density is discussed controversially. Diabetes mellitus due to an autoimmune process seems to be associated with low turnover osteopenia either in the animal model or in children and adolescents. A number of factors are discussed as being involved, but in this age group clinical symptoms are missing. Adult patients of either sex with IDDM show a reduced bone mineral density when measured at peripheral sites such as the distal forearm or the femoral neck, diabetic complications such as neuropathy and microangiopathy seem to pronounce the deficit of bone mass. In these patients, osteopenia is accompanied by a high turnover si…

Effect of vildagliptin compared to glimepiride on postprandial proinsulin processing in the β cell of patients with type 2 diabetes mellitus

This study compared the effect of Glimepiride versus Vildagliptin on β-cell function and the release of intact proinsulin (PI) in patients with type 2 diabetes mellitus. Patients on metformin monotherapy were randomized to add on treatment with Vildagliptin or Glimepiride. A standardized test meal was given at baseline, after 12 and 24 weeks of treatment. Insulin, PI and blood glucose values were measured in the fasting state and postprandial for 300 min. Fasting PI levels significantly decreased in the Vildagliptin group. The area under the curve for the postprandial release of PI decreased during Vildagliptin and increased during Glimepiride treatment. The proinsulin to insulin ratio decl…

Increased Arterial Augmentation and Augmentation Index as Surrogate Parameters for Arteriosclerosis in Subjects with Diabetes Mellitus and Nondiabetic Subjects with Cardiovascular Disease

Background: Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to compare these parameters in diabetic subjects and nondiabetic cardiovascular risk subjects with healthy control subjects. Methods: One hundred sixty-six nonsmoking subjects aged between 35 and 70 years were included in the study, which included 100 subjects with cardiovascular disease but not diabetes (mean age 62.73±8.75 years), 33 subjects with type 2 diabetes (66.58±2.69 years), and 33 healthy controls (51.89±8.91 years). In these subjects, arterial stiffness was measured by the diff…

Impact of insulin on microvascular blood flow and endothelial cell function in the postprandial state in patients with Type 1 diabetes.

The aim of the present study was to investigate postprandial microvascular blood flow following a standardized test meal in nondiabetic subjects and in patients with Type 1 diabetes after regular insulin or insulin lispro. In this open-label, randomised cross-over study, 20 nondiabetic participants and 20 patients with Type 1 diabetes were enrolled. To valuate the postprandial time course of skin microvascular blood flow, laser Doppler flux (LDF) readings were obtained at baseline and every 30 min following a standardized test meal. Furthermore, the microvascular response to acetylcholine (Ach) was measured, and blood was collected for the measurement of serum insulin and blood glucose leve…

40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Auswahl richtet sich nach Evidenz und potenziellen Nebeneffekten

Die schmerzhafte diabetische Polyneuropathie (DPN) ist eine schwerwiegende Komplikation eines Diabetes mellitus. Sie schrankt die Lebensqualitat der betroffenen Patienten stark ein. Eine effektive Therapie bei schmerzhafter DPN ist fur Patienten und Therapeuten eine Herausforderung. Viele mehr oder minder gut untersuchte Medikamente werden hierbei eingesetzt. Aber lediglich fur Duloxetin, Gabapentin und Pregabalin liegt eine spezifische Zulassung in dieser Indikation vor. Die schmerzreduzierenden Eigenschaften dieser Substanzen sind laut einer kurzlich publizierten Metaanalyse ahnlich, sodass sich die Auswahl an den zu erwartenden Nebenwirkungen orientieren sollte.

Sequential Treatment Escalation with Dapagliflozin and Saxagliptin Improves Beta Cell Function in Type 2 Diabetic Patients on Previous Metformin Treatment: An Exploratory Mechanistic Study

AbstractWe investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5±7.0 years; duration of diabetes 8.8±4.7 years; HbA1c 63.9±15.8 mmol/mol; mean±SD) were enrolled in the study. During a first treatment period (TP1) all patients received 10 mg dapagliflozin for one month, followed by the addition of 5 mg saxagliptin or placebo for another month (TP2). At baseline and at the end of each treatment period, fasting glucose and insulin levels were analysed, and a hyperglycaemic clam…

The influence of advanced glycation endproducts (AGE) on the expression of human endothelial adhesion molecules.

Advanced glycation endproducts (AGEs) possibly play a dominant role in the pathogenesis of macrovascular disease in diabetes. Recent studies could demonstrate that glycated albumin (AGE-BSA) was able to stimulate vascular cell adhesion molecule-1 (VCAM.1) on endothelial cells. The aim of this study was to find out if AGE-BSA was not only able to enhance the expression of vascular cell adhesion molecule-1, but also of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin on human endothelial cells. Stimulation of endothelial cells with AGE-BSA for six hours predominantly increased the expression of VCAM-1, but ICAM-1 and E-Selectin were also upregulated as shown by immunoilluminometric a…

Elevated serum leptin concentrations in type 2 diabetic patients with microalbuminuria and macroalbuminuria

Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A…

Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+,K+-ATPase activity in diabetes mellitus type I

This study was conducted to evaluate the influence of proinsulin C-peptide on erythrocyte Na(+),K(+)-ATPase and endothelial nitric oxide synthase activities in patients with type I diabetes. In a randomized double-blind study design, ten patients with type I diabetes received intravenous infusions of either human C-peptide or physiological saline on two different occasions. C-peptide was infused at a rate of 3 pmol.min(-1).kg(-1) for 60 min, and thereafter at 10 pmol.min(-1).kg(-1) for 60 min. At baseline and after 60 and 120 min, laser Doppler flow (LDF) was measured following acetylcholine iontophoresis or mild thermal stimulation (44 degrees C), and venous blood samples were collected to…